A NEW JOURNEY OF HU PROTEIN FAMILY

Alternative splicing is a general mechanism in §higher eukaryotic organisms to increase their§diversity. In contrast to its importance, the§mechanism of alternative splicing regulation is§poorly understood, especially in the nervous system,§where extensive alternative splicing occurs. During§my Ph.D. study, I identified a family of novel§neuron-specific splicing regulators, Hu proteins. My§studies provided solid evidence that support the§splicing regulatory function of Hu proteins. Two§genes that undergo neuron-specific splicing were used§as model in my research: calcitonin/CGRP and NF1. In§calcitonin/CGRP gene model, Hu proteins inhibit the§recognition of the non-neuronal exon by two§mechanisms: blocking the positive splicing factors§TIA-1/R and suppressing polyadenylation. NF1 is a§well-studied tumor suppressor, and the§neuron-specific skipping of exon 23a has been§reported to change its activity. My research§demonstrated that Hu proteins strongly suppress§recognition of exon 23a by the splicing machinery in§neurons. In summary, my research has contributed§significantly to the understanding of the§splicing regulation in neurons.